Hurricane Matthew impacted eastern North Carolina during October 2016. A regional after-action exercise was conducted as a moderated discussion using an adaptation of Federal Emergency Management Agency's (FEMA's) after-action report format to allow health departments to communicate lessons learned across jurisdictional lines. Forty-one professionals from 18 counties participated in a 2-hour workshop. Information on strengths, weaknesses, and recommendations was collected in small-group format, organized into county clusters by hazard mitigation regions and by 3 professional roles (health director, nursing director, and preparedness coordinator). Interagency agreements varied by county, depending on regularity of hurricanes and flooding. Improvement opportunities included enhanced coordination with American Red Cross in shelter operations and opening more special medical needs shelters. Participants emphasized successful coordination with county emergency management leaders. A regional after-action exercise designed as a moderated workshop focusing on the public health response provided an opportunity to exchange strengths and lessons learned after Hurricane Matthew in eastern North Carolina. This after-action approach may be useful for similar local health jurisdictions to build regional consensus for future disaster response planning and training.